This is not all they report as they also discuss various controls and other observations about these mice and their brains and their responses to the antibiotic treatment.

But what they do not report on is any evidence of anything other than a correlation between the GI microbiome changes and the inflammatory markers and the reduced Aβ plaque deposition. They even state this VERY BRIEFLY in their paper

We are fully cognizant of the fact that the findings reported herein are purely correlative and do not elucidate precise mechanism(s).

Yet then through other papers parts of the paper they misstate what they find and somehow, almost magically, turn this correlation into evidence for a causative connection. For example in the abstract

No. These findings are consistent with that. They are also consistent with, for example, the antibiotics affecting microbes in the brain which in turn could affect inflammatory markers. Or microbes on the skin. Or in the blood. Or elsewhere. I don't see any evidence here for a causative connection between the gut microbes (which are certainly affected by these antibiotics) and the plaque.

Yet even worse is that this misrepresentation of a causative connection makes it into the title of the article

What? This "through changes in the gut microbiome" is just completely misrepresenting what was shown in the paper.

Here are some misleading parts of the PR

The study, published July 21, 2016, in Scientific Reports, also showed significant changes in the gut microbiome after antibiotic treatment, suggesting the composition and diversity of bacteria in the gut play an important role in regulating immune system activity that impacts progression of Alzheimer's disease.

Nope. Nope. and Nope.

Thankfully there are a few caveats in the PR too but that does not balance misleading statements. The worst is saved for the end

"There's probably not going to be a cure for Alzheimer's disease for several generations, because we know there are changes occurring in the brain and central nervous system 15 to 20 years before clinical onset," he said. "We have to find ways to intervene when a patient starts showing clinical signs, and if we learn how changes in gut bacteria affect onset or progression, or how the molecules they produce interact with the nervous system, we could use that to create a new kind of personalized medicine."

Basically, saying there will be a cure for Alzheimer's. And then saying if we learn HOW (not if) gut microbes affect onset or progression, then we can better cure or treat this disease. This is just too bold and misleading for my taste. Nice paper. Interesting work and implications. But it is misleading to say they have shown any causative connection between gut microbes and Alzheimer's in this paper and also very misleading to start to talk about how they will use this to lead to treatments or cures.

Oh, and did I mention this was in mice not humans? So how do they get from a correlative study in mice to how gut microbes affect progression of Alzheimer's in humans? Really this is not OK, even to hint at.

And of course, which such misleading material in their own paper and in their PR it is not surprising that some of the reporting on this is going awry.

And I am sure many more to come. Scientists have to be more careful with discussing and presenting the implications of their work. I love the microbiome field and the possible implications to me are enormous for the role of the microbiome in various areas of biology. But misrepresenting ones findings, especially when it comes to human diseases, is dangerous and bad for science and bad for the microbiome field. The author's of the paper and the people behind the PR at the University of Chicago should publish a correction of the PR and also publish a correction of their paper to correct the misleading representations. And for their misleading material in their paper and in the PR I am giving them a coveted "Overselling the Microbiome" award.

Thursday, July 14, 2016

I am continually torn about handing out "overselling the microbiome" awards to many "stories" that are coming out recently on new scientific studies. On the one hand, many of these studies are quite interesting. On the other hand, a huge number of them oversell the implications of the work. And for some reason it seems to me that studies that could indicate a positive role for microbes in some way seem to end up with more misrepresentation than other types of work. Mind you, I truly believe the cloud of microbes living in and on various plants and animals are likely to play fundamental roles in all sorts of important functions. But my thinking this and my thinking it is likely does not mean we should go around overstating the implications of work in this area.

Interesting. But a key part of this is that they discovered a correlation. Lots and lots and lots of possible explanations for this correlation including some examined in the paper but none of which have been proven. Some news reports do a good job of covering the topic and discussing how this is still just a correlative observation. For example see this Washington Post article by Lateshia Beachum. There they report on the authors comments where the authors seem to think this supports the hygiene hypothesis

“The findings support the ‘hygiene hypothesis,’ which suggests that being exposed to microbes as a child reduces your risk of developing allergies,” Hancox said in a statement.

But then immediately this is countered by some more careful thoughts

Hirsh Komarow, a staff clinician at the National Institute of Allergy and Infectious Diseases, isn’t entirely convinced about the study’s conclusions. “It’s an interesting observation, but it needs more analysis,” Komarow said.

And then he is further quoted with other possible explanations

Komarow also suggested that thumb-sucking and nail-biting could be indicative behaviors that either thwart or encourage allergic reactions. He said being part of a large family and being exposed to microbes from many siblings may affect a child’s allergic sensitization.

And there are other articles out there with a decent amount of caveating. But sadly the New York Times article by Perri Klass is not so tempered. Here are some of what I consider to be statements without enough caveating or countering:

A new study suggests that those habits in children ages 5 to 11 may indeed increase exposure to microbes, but that that may not be all bad.

No no no. The new study did not suggest that. The new study is consistent with that, but it is consistent with many other explanations.

And then there is this:

These differences could not be explained by other factors that are associated with allergic risk. The researchers controlled for pets, parents with allergies, breast-feeding, socioeconomic status and more. But though the former thumb-suckers and nail-biters were less likely to show allergic sensitization, there was no significant difference in their likelihood of having asthma or hay fever.

Well it is nice that the authors of the paper tested for some other possible explanations. But it is a giant and inappropriate leap to go from that to "These differences could not be explained by other factors that are associated with allergic risk"

And then there are multiple quotes from the authors which are not really caveated enough or at all

Robert J. Hancox, one of the authors of the study, is an associate professor in the Department of Preventive and Social Medicine at Dunedin School of Medicine, a department that is particularly oriented toward the study of diseases’ causes and risk factors. He said in an email, “The hygiene hypothesis is interesting because it suggests that lifestyle factors may be responsible for the rise in allergic diseases in recent decades. Obviously hygiene has very many benefits, but perhaps this is a downside. The hygiene hypothesis is still unproven and controversial, but this is another piece of evidence that it could be true.”

Some caveats here but not enough. This is not "evidence that it could be true" but rather it is data consistent with that model, but also consistent with other models that have nothing to do with the hygiene hypothesis.

And then there is this:

Malcolm Sears, one of the authors of the paper, a professor of medicine at McMaster University in Hamilton, Ontario, who was the original leader for the asthma allergy component of the New Zealand study, said, “Early exposure in many areas is looking as if it’s more protective than hazardous, and I think we’ve just added one more interesting piece to that information.”

No this study did not show that early exposure from thumb sucking or nail biting has any protective benefit. It showed a correlation between thumb sucking/nail biting and lower risk of sensitization. It did not show any causal connection. And even if a causal connection were found, one would still have to test for what was the mechanism and the mechanism could be many things unconnected to microbial exposure.

And then there is this

Dr. Hancox pointed out that the study does not show any mechanism to account for the association. “Even if we assume that the protective effect is due to exposure to microbial organisms, we don’t know which organisms are beneficial or how they actually influence immune function in this way.”

Yes, this is good in some ways. But why would we assume this? Stating this without caveats makes it seem like we should assume this.

and

Dr. Sears said, “My excitement is not so much that sucking your thumb is good as that it shows the power of a longitudinal study.” (A longitudinal study is one that gathers data from the same subjects repeatedly over a period of time.) And in fact, as researchers tease out the complex ramifications of childhood exposures, it’s intriguing to look at long-term associations between childhood behavior and adult immune function, by watching what happens over decades.

None of these quotes are really caveating the claims. And then the article ends with a statement that seems to indicate that this is all a proven fact

So perhaps the results of this study help us look at these habits with slightly different eyes, as pieces of a complicated lifelong relationship between children and the environments they sample as they grow, which shape their health and their physiology in lasting ways.

Yes, this study is interesting. And yes, it might be indicative of a causative connection between exposure to microbes on thumbs and nails and reducing risk to allergy. But no, the study did not show that there is a causative connection, just a correlation. And thus we cannot conclude at this point that we should "look at these habits with slightly different eyes, as pieces of a complicated lifelong relationship between children and the environments." The correlation could be due to other factors that have nothing to do with these habits. And this is just a massive difference. Shame on the New York Times for not reporting on this carefully enough.

And thus I am awarding a coveted Overselling the Microbiome Award to the New York Times and Perri Klass.

International travel presenter Ian Wright is on a mission to seek out and lick the dirtiest locations in Europe for The Lick-hiker’s Guide to Inner Strength, a campaign that promotes the virtues of Gefilus, a good bacteria product range by dairy giant, Valio.

Simultaneously almost certainly over-promoting the benefits of this one probiotic and also the risks of licking things all over the globe.

Our 25-minute documentary sees Wright’s tongue come into contact with places that harbour bad bacteria - all in the name of testing immunity, gut health, and science. These include a metro station, public toilet, telephone, kindergarten, river, €10 note, bronze statue and Tottenham Hotspur FC.

Did they really have to pick on Tottenham?

Valio commissioned hasan & partners to demonstrate the power of Gefilus, which contains the friendly Lactobacillus rhamnosus GG and vitamins. Lactobacillus rhamnosus GG is the world’s most researched lactic acid bacterium and its qualities have since been scrutinized in more than 800 scientific studies globally.

Umm - just because there are 800 papers does not mean it is necessarily good for you. I mean, published papers is a good thing. But there are also 1000s of papers on anthrax and smallpox ...

Armed with bottles of good bacteria and a luminometer to count germs, the two-week tongue tour of Europe tests Wright’s taste buds and nerve to the limit. Viewers will find out if he survived the ordeal without contracting any stomach bugs and where in the world is the location with the worst bacterial score.

OK - well then. A luminometer will reveal everything you need to know about a sample of microbes. We should just use them for every microbial study everywhere (nothing against luminometers per se, but they really are not what is needed here).

Jussi Lindholm, COO of hasan & partners, comments: "Good bacteria in Gefilus products has been carefully studied and people believe in it. But seeing is believing, so the documentary is both educational and fun, designed to physically draw attention to the link between the gut, our inner strength, and our wellbeing. World traveller Ian Wright has experienced many challenges and Gefilus was probably the weirdest."

"And in an editorial that will appear on 11 July in eight of its journals, the American Society for Microbiology in Washington DC will announce plans to remove the impact factor from its journals and website, as well as from marketing and advertising.

“To me, what’s essential is to purge the conversation of the impact factor,” says ASM chief executive Stefano Bertuzzi, a prominent critic of the metric. “We want to make it so tacky that people will be embarrassed just to mention it.”

This is in relation to the recent preprint I posted about a few minutes ago ...

This paper in BioRXiv is definitely worth checking out.
Abstract is below:

Although the Journal Impact Factor (JIF) is widely acknowledged to be a poor indicator of the quality of individual papers, it is used routinely to evaluate research and researchers. Here, we present a simple method for generating the citation distributions that underlie JIFs. Application of this straightforward protocol reveals the full extent of the skew of distributions and variation in citations received by published papers that is characteristic of all scientific journals. Although there are differences among journals across the spectrum of JIFs, the citation distributions overlap extensively, demonstrating that the citation performance of individual papers cannot be inferred from the JIF. We propose that this methodology be adopted by all journals as a move to greater transparency, one that should help to refocus attention on individual pieces of work and counter the inappropriate usage of JIFs during the process of research assessment.

Thursday, July 07, 2016

Well this is disappointing. Was googling for a person and found this Agilent "Thought Leaders Program". It is described as

This invitational program promotes fundamental scientific advancements by contributing financial support, products and expertise to the research of influential thought leaders in the life sciences, diagnostics, and chemical analysis.

Alas it might be described better as "Agilent Male Thought Leaders Program". In my estimation (based on the pronouns used in the descriptions of the people and in Googling around for more information), of the 31 "thought leaders" 28 are male. That comes to a bit more than 90%. It seems like there is some sort of bias here. Agilent should and could do better.

Sunday, July 03, 2016

An influential article in my career development was this piece on the Washington Post in 1996 by Stephen Jay Gould. I was already convinced bacteria were important and interesting. But it was nice to see the person who got me interested in evolution (via his books and then a class I took from him in college) emphasizing the bacteria. Here is a link to the Post archive of it.

Well, my mom sent me a copy of it and I kept it all these years. Just scanned it so, I thought I would share what it looked like in the paper since this is VERY different from looking at the text on the Post archive site.

I like the last part too - an ad for the American Society for Microbiology that went with the article.